The sialotranscriptomes of
Aedes aegypti revealed a transcript overexpressed in
female salivary glands that
codes a mature 7.8 kDa
peptide. The
peptide, specific to the
Aedes genus, has a unique sequence, presents a putative secretory
nature and its function is unknown. Here, we confirmed that the
peptide is highly expressed in the
salivary glands of
female mosquitoes when compared to the
salivary glands of
males, and its
secretion in
mosquito saliva is able to sensitize the
vertebrate host by inducing the
production of specific
antibodies. The synthetic version of the
peptide downmodulated
nitric oxide production by activated peritoneal murine
macrophages. The fractionation of a Ae. aegypti salivary preparation revealed that the fractions containing the naturally secreted
peptide reproduced the
nitric oxide downmodulation. The synthetic
peptide also selectively interfered with
cytokine production by murine
macrophages, inhibiting the
production of
IL-6,
IL-12p40 and CCL2 without affecting TNF-α or
IL-10 production. Likewise, intracellular
proteins associated with
macrophage activation were also distinctively modulated while iNOS and NF-κB p65 expression were diminished, IκBα and
p38 MAPK expression did not change in the presence of the
peptide. The anti-inflammatory properties of the synthetic
peptide were tested in vivo on a
dextran sulfate sodium-induced
colitis model. The
therapeutic administration of the Ae. aegypti
peptide reduced the
leukocytosis,
macrophage activity and
nitric oxide levels in the gut, as well as the expression of
cytokines associated with the
disease, resulting in amelioration of its clinical signs. Given its
biological properties
in vitro and in vivo, the molecule was termed
Aedes-specific MOdulatory
PEptide (AeMOPE-1). Thus, AeMOPE-1 is a novel
mosquito-derived immunobiologic with potential to treat immune-mediated disorders.